With 5 decades of prospectively collected risk factor data and more than 1070 initial completed strokes documented in the community-based Framingham Heart Study (FHS), the Precursors of Stroke Incidence and Prognosis (PSIP) project is well positioned to focus on current issues confronting pathogenesis and prevention of stroke. This study will further understanding of the epidemiology of stroke through identification of newer risk factors and genetic influences. Another 5 years of follow-up will also allow more precise determination of lifetime risk, secular trends, and outcomes of ischemic stroke and ischemic stroke subtypes as well as intracerebral and subarachnoid hemorrhages. Added to these data are measures of subclinical cerebrovascular disease previously identified on quantitative brain MRI scans on 2,484 Offspring and Omni [unreadable] subjects. Inclusion of novel risk factors, particularly inflammatory markers, enlarges this investigation beyond traditional risk factors and highlights new links to incident stroke and to subclinical cerebrovascular disease. Subclinical indicators of atherosclerosis - MRI of the heart and aorta, CT measures of coronary and aortic calcification, cardiac echocardiography and carotid ultrasonography will also be related to stroke incidence and manifestations. Systematic assessment of clinical, functional and cognitive outcome following stroke increases prospective surveillance beyond 20 years, providing the basis for determining lifetime risk and secular trends for subtypes of stroke. Capitalizing on the extensive family structure of the FHS, this continuation will extend the PSIP study to the newly recruited grandchildren of the Original Framingham cohort (Gen3) and children of the Omni cohort (Omni Gen2). Familial aggregation of stroke, clinical and subclinical, will be studied utilizing the rich multigenerational family based structure. Genome scans and extensive genotyping is available on a large number of subjects thereby facilitating association studies to identify genes contributing to the qualitative traits of stroke. Clinical and subclinical stroke in the Offspring will be related to documented stroke in parents and siblings to assess the impact of stroke risk factors depending on family history of stroke. [unreadable] [unreadable]